Current evidence suggests that remyelination plays an important role in recovery from acute attacks of multiple sclerosis (MS). A variety of immunosuppressive, antimitotic and anti-inflammatory drugs are currently being used in the treatment of multiple sclerosis either routinely or in therapeutic trials. These drugs include ACTH, prednisone, dexamethasone, azathioprine, cyclophosphamide and cyclosporin. While the immunosuppressive characteristics of these compounds are well known, the fact that these drugs can inhibit demyelination and inhibit or enhance remyelination is little known and has not been adequately studied. A clear understanding of the effects of these drugs on remyelination, the timing of these effects, and the mechanisms involved could suggest new approaches to the treatment of MS and provide a better rationale for the use of existing drugs and drug combinations. Thus, the information obtained could have a profound effect on the planning of new clinical trials in multiple sclerosis. In preliminary studies, we have shown that remyelination can be significantly inhibited or enhanced. Steroids can both reduce demyelination and significantly inhibit remyelination. With certain treatment schedules, azathioprine and cyclophosphamide can enhance remyelination, producing as much as a 50% increase in myelin thickness four weeks after demyelination by lysolecithin. The purpose of this project is to examine the effects of these drugs on both the extent of demyelination following a lysolecithin lesion and on the rate and ultimate extent of remyelination. The results of these studies should lead to a better understanding of the effects of these drugs on the clinically important problem of remyelination following attacks of MS and should contribute to improvements in the design of drug schedules for therapeutic trials.